Medium-ring natural products exhibit diverse biological activities but such scaffolds are underrepresented in probe and drug discovery efforts due to the limitations of classical macrocyclization reactions. We report herein a tandem oxidative dearomatization-ring-expanding rearomatization (ODRE) reaction that generates benzannulated medium-ring lactams directly from simple bicyclic substrates. The reaction accommodates diverse aryl substrates (haloarenes, aryl ethers, aryl amides, heterocycles) and strategic incorporation of a bridgehead alcohol generates a versatile ketone moiety in the products amenable to downstream modifications. Cheminformatic analysis indicates that these medium rings access regions of chemical space that overlap with related natural products and are distinct from synthetic drugs, setting the stage for their use in discovery screening against novel biological targets.
Synthesis of Benzannulated Medium-ring Lactams via a Tandem Oxidative Dearomatization-Ring Expansion Reaction
Posted by
Derek S. Tan
on 12 09 2019
Related content
19 04 2023
< 1 minute
Predicting pKa
One of the most important physicochemical properties of small molecules and macromolecules are the...
12 05 2022
< 1 minute
Coupling stabilizers open KV1-type potassium channels
ABSTRACT: The opening and closing of voltage-gated ion channels are regulated by voltage sensors...
13 12 2021
< 1 minute
Cheminfo Stories 2021 Virtual UGM Asia Pacific Edition: Design of new compounds from the available chemical space
In computational compound design workflows, the analysis of the available chemical space is an...
12 11 2021
< 1 minute
Responding to the Challenge Posed by the Generic Control of Substances
Drug monitoring organizations report that new psychoactive substances continue to emerge, posing...